French guidelines for the diagnosis and management of Tourette syndrome.

The term "Gilles de la Tourette syndrome", or the more commonly used term "Tourette syndrome" (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment.

Validation of a non-motor fluctuations questionnaire in Parkinson's disease.

INTRODUCTION: Non-motor fluctuations (NMF) in Parkinson's disease (PD) remain poorly recognized but have a high impact on patients' quality of life. The lack of assessment tools limits our understanding of NMF, compromising appropriate management. Our objective was to validate a hetero-questionnaire for NMF in PD patients at different stages of the disease: without treatment, without motor fluctuations, with motor fluctuations. METHODS: We included patients in 15 centers in France. Our questionnaire, NMF-Park, resulted from previous studies, allowing us to identify the more pertinent NMF for evaluation. Patients reported the presence (yes or no) of 22 selected NMF, and their link with dopaminergic medications. The assessment was repeated at one and two years to study the progression of NMF. We performed a metrological validation of our questionnaire. RESULTS: We included 255 patients (42 without treatment, 88 without motor fluctuations and 125 with motor fluctuations). After metrological validation, three dimensions of NMF were found: dysautonomic; cognitive; psychiatric. The sensory/pain dimension described in the literature was not statistically confirmed by our study. DISCUSSION: Our questionnaire was validated according to clinimetric standards, for different stages of PD. It was clinically coherent with three homogeneous dimensions. It highlighted a link between fatigue, visual accommodation disorder, and cognitive fluctuations; and the integration of sensory/pain fluctuations as part of dysautonomic fluctuations. It focused exclusively on NMF, which is interesting considering the described differences between non-motor and motor fluctuations. CONCLUSION: Our study validated a hetero-questionnaire of diagnosis for NMF for different stages of PD.

Prevalence and characterisation of vocal fold motion impairment (VFMI) in patients with Multiple system atrophy compared with Parkinson's disease.

INTRODUCTION: Multiple system atrophy (MSA) is a neurodegenerative disorder in which vocal fold mobility can be affected, sometimes leading to life-threatening situations. Our aim was to know if laryngeal examination could help differentiate MSA from Parkinson's disease (PD). MATERIALS AND METHODS: Between 2004 to 2014, all consecutive patients diagnosed with probable MSA were included in this retrospective, monocentric study. Flexible laryngoscopy was obtained in 51 MSA patients and compared with 27 patients with Parkinson's disease (PD). Laryngeal muscles EMG was available in 6 MSA patients. RESULTS: Vocal fold motion impairments (VFMI) was found in 35 (68.6%) MSA patients: 15 (29.4%) had uni- or bilateral vocal fold abnormal movement (VFAM), 13 (25.5%) had uni- or bilateral vocal fold abductor paresis (VFABP), 4 (7.8%) had uni- or bilateral vocal fold adductor paresis (VFADP), 10 (19.6%) had bilateral vocal fold paralysis (BVFP). VFMI was found in 13 PD patients (48.1%) all of whom had VFADP. Presence of BVFP was found associated with stridor (P<0.001) and dysphagia (P=0.002). In all muscles examined in 6 MSA patients, the EMG showed neuropathic patterns. CONCLUSIONS: Our data support that VFMI may be encountered in two-thirds of MSA with a variable degree of gravity. Laryngological examination should be considered as a supplementary tool for the diagnosis and prognosis of MSA. VFMI in particular VFAM, VFABD and BVFP should be discussed as an additional possible red flag even at an early stage of MSA and could help discriminate MSA from PD.

Pretherapeutic functional neuroimaging predicts tremor arrest after thalamotomy.

OBJECTIVE: Essential tremor (ET) represents the most common movement disorder. Drug-resistant ET can benefit from standard stereotactic procedures (deep brain stimulation or radiofrequency thalamotomy) or alternatively minimally invasive high-focused ultrasound or radiosurgery. All aim at same target, thalamic ventro-intermediate nucleus (Vim). METHODS: The study included a cohort of 17 consecutive patients, with ET, treated only with left unilateral stereotactic radiosurgical thalamotomy (SRS-T) between September 2014 and August 2015. The mean time to tremor improvement was 3.32 months (SD 2.7, 0.5-10). Neuroimaging data were collected at baseline (n = 17). Standard tremor scores, including activities of daily living (ADL) and tremor score on treated hand (TSTH), were completed pretherapeutically and 1 year later. We further correlate these scores with baseline inter-connectivity in twenty major large-scale brain networks. RESULTS: We report as predictive three networks, with the interconnected statistically significant clusters: primary motor cortex interconnected with inferior olivary nucleus, bilateral thalamus interconnected with motor cerebellum lobule V2 (ADL), and anterior default-mode network interconnected with Brodmann area 103 (TSTH). For all, more positive pretherapeutic interconnectivity correlated with higher drop in points on the respective scores. Age, disease duration, or time-to-response after SRS-T were not statistically correlated with pretherapeutic brain connectivity measures (P > .05). The same applied to pretherapeutic tremor scores, after using the same methodology described above. CONCLUSIONS: Our findings have clinical implications for predicting clinical response after SRS-T. Here, using pretherapeutic magnetic resonance imaging and data processing without prior hypothesis, we show that pretherapeutic network(s) interconnectivity strength predicts tremor arrest in drug-naïve ET, following stereotactic radiosurgical thalamotomy.

Essential tremor: Update of therapeutic strategies (medical treatment and gamma knife thalamotomy).

Tremor is a highly prevalent movement disorder that markedly reduces quality of life. The management of severe tremor is particularly challenging. Pharmacological treatment is available, but no real breakthrough has emerged recently. Propranolol and primidone are still the two most recommended agents, followed by topiramate. However, surgical treatments for medically refractory tremors are expanding. Gamma knife (GK) thalamotomy is an option particularly suitable for patients who are not candidates for deep brain stimulation. Owing to the fact that it is a non-invasive procedure without craniotomy, GK radiosurgery has almost no contraindications. Since the late 1990s, more than 250 case reports and patient series have been published. Most of these studies show that unilateral GK thalamotomy is well tolerated and reduces tremor disability. A recent study with prospective blinded assessment has confirmed its safety, together with significant improvements in tremor scores and activities of daily living.

News and controversies regarding essential tremor.

Essential tremor is the most common movement disorder in adults. It is characterized by a postural and kinetic tremor affecting the arms, but it can also affect other body parts. It evolves gradually and can be responsible for a functional impairment in activities of daily living. Its pathophysiology remains poorly understood and effective therapeutic options are limited. There are significant semiological variations between patients, and the term "essential tremor" seems to encompass a wide range of heterogeneous clinical phenotypes. The diagnostic criteria presented in 1998 are now challenged. Furthermore, there is a current debate concerning the etiology of this affection, as to whether essential tremor is a complex degenerative disorder or a functional reversible disorder of neuronal oscillation. In this review, we summarize some aspects of clinical, etiologic and therapeutic news, to better address the questioning on unravelling the clinical presentation and examine the current pathophysiological controversy in this disorder.

Controlled general anaesthesia for subthalamic nucleus stimulation in Parkinson's disease.

OBJECTIVE: To report the short-term (1 year) and long-term (5 years) outcome of patients with Parkinson's disease (PD) with subthalamic nucleus (STN) stimulation operated upon under controlled general anaesthesia (GA). METHODS: 213 consecutive patients with PD were included between January 2000 and March 2009 and operated upon under a particular type of GA with close control of the level of sedation allowing intraoperative recordings. 188 patients were assessed 1 year postoperatively. 65 patients also completed the long-term observation period and were evaluated 5 years postoperatively. RESULTS: The Unified PD Rating Scale III score in the 'Off drug--On stim' condition was improved at 1 year and 5 years by 61% and 37%, respectively, (p<0.001). Motor complications decreased at short-term and long-term by 68% and 65%, respectively, for dyskinesia and by 52% and 48%, respectively, for fluctuations, (p<0.001). Dopaminergic treatment could also be reduced at short-term and long-term by 46% and 49%, respectively (p<0.001). There was no significant modification of mood and cognition assessments (Mattis scale and Beck depression inventory) at 1 year and 5 years. Concerning the main adverse events related to the surgery, we report four haematomas (1.9%) with two deaths (0.9%), eight cases of transient confusion (3.7%) and no epileptic seizure. CONCLUSIONS: Our results confirm that STN stimulation performed under controlled GA is efficient and has similar short-term and long-term motor effects than intervention under local anaesthesia. Furthermore, this specific procedure is not associated with more adverse events. The success of such an intervention requires strict anaesthetic monitoring and accurate STN identification.

[Transcutaneous tibial nerve stimulation in the overactive bladder syndrome in patients with Parkinson's syndromes]. / Stimulation transcutanée chronique du nerf tibial dans l'hyperactivité vésicale des syndromes parkinsoniens.

OBJECTIVES: To evaluate the efficacy of chronic transcutaneous tibial nerve stimulation (TNS) on overactive bladder syndrome in female patients with Parkinson's disease (PD) and multiple system atrophy (MSA). PATIENTS AND METHODS: A prospective monocentric study enrolled six female patients with PD or MSA suffering from overactive bladder syndrome for a six-week study period. Daily sessions of 20 minutes of TNS were provided. The primary outcome measurement was the Patient Global Impression of Improvement (PGI-I scale). The secondary outcomes measurements were symptom and quality of life scores, bladder diary and urodynamics. The outcomes after 6 weeks of TNS were compared to baseline. RESULTS: TNS was considered as an effective treatment by five patients out of six (83%) who ask to pursue the treatment and were still doing it 6 months after the end of the study. A trend improvement was observed in only two of the secondary evaluation criteria the V8 median score 21/40 to 14/40 (P=0.2) and the maximum cystometric capacity increased from 211 mL ± 106 to 260 mL ± 226 (P=0.6) after SNT. CONCLUSION: Although urodynamics and symptoms scores did not show significant difference, an efficacy of TNS on overactive bladder in PD and MSA is possible. Additional placebo controlled works enrolling more patients are required to ensure these preliminary results.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Addictive behaviors and Parkinson's disease.

INTRODUCTION: In Parkinson's disease, the degeneration of the dopaminergic system and the longstanding exposure to dopamine replacement therapy (DRT) may cause, in a group of vulnerable patients, dysregulation of the brain reward system. STATE OF THE ARTS: These patients develop DRT-related compulsions, which include addiction to levodopa or dopamine dysregulation syndrome (DDS), punding, and impulse control disorders (ICDs). ICDs or behavioral addiction reported in Parkinson's disease include pathological gambling, hypersexuality, compulsive buying and binge eating. Although the underlying pathophysiology is still poorly understood, these behaviors are linked by their reward-based and repetitive nature. Such behaviors may result in devastating psychosocial impairment for the patients and are often hidden. PERSPECTIVE AND CONCLUSIONS: The recognition of these behaviors is important and allows a better clinical management. Although the limited data do not permit particular therapeutic strategies, some approaches are worth considering: DRT reduction, trials of non-dopaminergic medications and subthalamic chronic stimulation.

[Non-motor fluctuations in Parkinson's disease]. / Les fluctuations non motrices de la maladie de Parkinson.

Nonmotor fluctuations (NMF) in Parkinson's disease are nonmotor symptoms that occur in coincidence with motor fluctuations or independently. Long under-assessed, NMF are now recognized as frequent and sometimes involving a greater degree of disability than motor fluctuations. They can be classified in three categories: dysautonomic, cognitive/psychiatric and sensory/pain. Recognition of these nonmotor fluctuations as part of Parkinson's disease has important implications. Some symptoms such as dyspnea, chest pain, or abdominal pains can mimic cardiac or gastrointestinal emergencies. The underlying pathogenic mechanisms of NMF are not well known. The dopaminergic system is probably involved via modulation of other systems (serotoninergic, adrenergic) since NMF usually respond to dopaminergic treatment. Subthalamic nucleus deep brain stimulation alleviates NMF-- particularly sensory, dysautonomic and cognitive fluctuations--while psychic fluctuations respond less consistently to this treatment. The development of new instruments that enable a comprehensive and precocious assessment of NMF is important for optimized management of advanced Parkinson's disease.

Assessment of cortico-spinal tract impairment in multiple system atrophy using transcranial magnetic stimulation.

OBJECTIVE: Among Parkinsonian syndromes, pyramidal signs suggesting cortico-spinal impairment are a hallmark of multiple system atrophy (MSA). Although it is crucial to diagnose correctly this disease to choose the appropriate treatment, the available diagnostic criteria lack sensitivity. Cortical excitability patterns assessed by transcranial magnetic stimulation (TMS) do not differentiate Parkinsonian disorders. TMS using triple stimulation technique (TST) accurately detects cortico-spinal impairment. We hypothesized that this technique could detect such impairment in MSA patients. METHODS: The TST was applied along with single and paired-pulse TMS to 31 patients fulfilling the diagnostic criteria for MSA-P (n=10), MSA-C (n=4), progressive supranuclear palsy (PSP; n=6) and Idiopathic Parkinson's disease (IPD; n=11) and 11 control subjects. RESULTS: Single and paired-pulse TMS patterns did not differ between any patient group. The TST pattern was abnormal in five MSA-P, one MSA-C and one PSP patients but not in IPD patients or controls. The mean TST ratio for MSA-P (86.6%) was significantly different from IPD (99.1%; p<0.05) whereas ratios for MSA-C (92.1%) and PSP (93.3%) were not different from IPD or controls (99.5%). CONCLUSIONS: These results suggest that TST is effective to assess cortico-spinal impairment in MSA. SIGNIFICANCE: TST might be useful for the diagnosis of atypical Parkinsonism.

[Multiple strokes after chickenpox primo-infection in an adult]. / Accidents vasculaires cérébraux multiples et primo-infection varicelleuse chez un adulte.

INTRODUCTION: Chickenpox is considered as a high risk factor for developing stroke in childhood, but descriptions in adult are exceptional (only three cases reported, to our knowledge). CASE REPORT: A 37-year-old man presented with a chickenpox eruption, followed by a right parietal and a left occipital infarcts, associated with multiple lacunae. There was no coagulation disorder, no hypertension or cardiovascular disorder. Cerebral angiography showed an irregular narrowing of the right internal parietal artery and vascular defects in right parietal and left occipital areas. The diagnosis of VZV-related vasculitis was evoked. White cell count, serology and VZV PCR were negative in the cerebrospinal fluid. Clinical improvement was observed after treatment by corticosteroids and aciclovir. CONCLUSION: Chickenpox is a rare cause of cerebral vasculitis. Involvement of both medium and small vessels was present here, contrary to other adult case reports in the literature. Hematogenous dissemination of the virus responsible for cerebral vasculitis seems to be the most probable pathophysiological mechanism.

[Difficulties associated with Lambert-Eaton syndrome]. / Difficultés autour d'un syndrome de Lambert-Eaton.

INTRODUCTION: The diagnosis and treatment of the neurological paraneoplastic syndromes associated with lung cancer can pose a challenge both to general physicians and neurologists as well as pulmonologists. CASE REPORT: A 53 year-old heavy smoker presented with a Lambert-Eaton myasthenic syndrome (LEMS). Bronchoscopy was normal but radiological examinations revealed a lymph node in site 4R. The pathological diagnosis after mediastinoscopy was negative. Twenty-five months later, an opacity on chest X-ray led to a biopsy which revealed a squamous cell carcinoma. A lobectomy was performed for a pT2N0M0 lesion. A significant improvement of neurological symptoms was seen. The myasthenic syndrome reappeared 21 months later. A local and general relapse was diagnosed. The patient died 10 months later despite chemotherapy. CONCLUSION: LEMS occurs because of an immunological reaction against voltage-dependent calcium channels. LEMS is generally associated with small cell lung cancer occurring in three percent of cases. However, the case that we report shows the unusual association of LEMS with non small-cell lung cancer and highlights the difficulties associated in the management of this condition.

[Melanocytic meningitis and large congenital melanocytic naevus: neurocutaneous melanosis]. / Méningite mélanocytaire et naevus géant congénital: la mélanose neurocutanée.

Neurological symptoms in a patient with large congenital melanocytic naevus are highly suggestive of cerebromeningeal melanoma metastasis. The presence of melanocytic cells in cerebrospinal fluid confirms this diagnosis If their malignant nature is shared with cutaneous naevocytic cells. Conversely, neurocutaneous melanosis is diagnosed when benign melanocytosis meningitis is found in patients with multiple and/or large congenital melanocytic naevus, whether cutaneous naevus cells are benign or not, or when cerebrospinal fluid cells are malignant with benign cutaneous melanocytic naevus. We report the case of a young man aged 19 presenting with multiple and large congenital melanocytic naevus who experienced transcient neurological signs and increased intracranial pressure. Cerebral neuroimaging evoked meningeal infiltration which benign melanocytic nature was supposed on CSF analysis and confirmed by necropsy findings, only 3 month after neurological onset, leading to neurocutaneous melanosis diagnosis. This rare neuroectodermal dysembryoplasia finds expression in various neurological signs, depending on patient's age and leptomeningeal and/or cerebral proliferation localization. Lumbar puncture, cerebral scanography and MRI may help diagnosis, but only histological examination can prove neurocutaneous melanosis, more often by necropsy because of poor prognosis.

[Primary leiomyosarcoma of the cavernous sinus associated with Epstein-Barr virus in a kidney graft]. / Leiomyosarcome primitif du sinus caverneux associé au virus Epstein-Barr chez un greffé rénal.

Immunodeficient patients have an increased incidence of neoplasms, whether the immunodeficiency is due to genetic disorder, the acquired immunodeficiency syndrome (AIDS), or immunosuppressive therapy. Leiomyosarcoma (LMS) is a rare neoplasm, even if its incidence has increased because of AIDS. Less than fifteen cases were described after organ transplantation. An intracranial localization is exceptional (five cases in the literature) and was never described after organ transplantation, to our knowledge. Our present report focuses on a 45-year-old immunocompromised patient, who received immunosuppressive therapy for renal transplantation. He suffered from atypical peri-orbital headaches six months after transplantation and a mass involving the cavernous sinus was identified. Surgical biopsy was performed. Histologic examination revealed a LMS. Epstein-Barr virus was identified by quantitative polymerase chain reaction in the LMS. Immunosuppression was reduced, the patient received adriamycin and protontherapy was realized. He died two years after the transplantation because of tumor progression and kidney failure.

[Neuroplasticity and Parkinson's disease] / Neuroplasticité et maladie de Parkinson.

Emerging concept, to date, neuroplasticity becomes a concrete reality in the adult central nervous system (CNS), particularly in a so-called neurodegenerative disease as idiopathic Parkinson's disease (IPD). After a brief survey of some general aspects of plasticity in the CNS, the present tutorial review illustrates with recent data from the literature the modes of plastic changes during the course of IPD, either resulting from dopaminergic denervation (hyperactivity of remaining dopaminergic neurons with increase of their excitatory cholinergic innervation in the substantia nigra, enhancement of the corticostriatal glutamatergic synaptic activity at the striatal level) or due to dopaminergic treatment (change in phosphorylation state of the striatal glutamate receptors, internalization of D1 Dopamine receptors). Neuroplasticity in Parkinson's disease could represent a rational basis for forthcoming therapeutic issues